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Biomedical subjects

Jeffry A Katz

Publications and source records attributed to Jeffry A Katz.

12 recordsLinked to original sources
PubMed2006

TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn's disease.

The CD40/CD40 ligand (CD40L) pathway is involved in Crohn's disease (CD) pathogenesis. In the patients' circulation, soluble CD40L (sCD40L) levels are elevated and surface CD40L is increased in platelets and T cells, whereas in the intestine CD40 is overexpressed in the microvasculature and CD40L in platelets and T cells. The therapeutic effects of infliximab in CD are attributed to its systemic anti-TNF-alpha action, but because TNF-alpha modulates both CD40 and CD40L, we investigated whether infliximab affects the CD40/CD40L pathway in the intestine. Eighteen CD patients were evaluated before and after infliximab therapy. Plasma sCD40L was measured by ELISA and platelet and peripheral blood T cell (PBT) CD40L expression by flow cytometry. Microvascular CD40 and VCAM-1 expression were assessed in mucosal biopsies by immunohistochemistry and by flow cytometry in human intestinal microvascular endothelial cells (HIMEC). Cell cultures were performed in the presence and absence of infliximab. Infliximab treatment significantly reduced plasma sCD40L levels and eliminated CD40 and VCAM-1 from mucosal microvessels. In vitro infliximab prevented TNF-alpha-induced CD40 and VCAM-1 expression by HIMEC, and reduced PBT, but not platelet, surface CD40L expression and sCD40L release. In addition, infliximab decreased T cell-induced VCAM-1 expression in HIMEC by down-regulating CD40L in T cells and promoting T cells apoptosis. These findings point to a novel mechanism of action of infliximab, i.e., the disruption of CD40/CD40L-dependent cognate interactions between intestinal microvessels and T cells. Thus, in addition to neutralizing TNF-alpha and inducing T cell death, the therapeutic effects of infliximab in CD appear to be also mediated by inhibition of vascular inflammation in the gut.

Adult↗
PubMed2006

Probiotics and prebiotics for gastrointestinal infections.

There is growing interest in and knowledge about the potential health-promoting benefits of both probiotics and prebiotics. Multiple mechanisms of action for the beneficial effect of probiotics and prebiotics have been postulated, including prevention of pathogenic bacteria growth, production of antimicrobial agents, stimulation of mucosal barrier function, and altering immunoregulation. Clinical trials support the efficacy of probiotics in the treatment of acute infectious diarrhea, the prevention of antibiotic associated diarrhea, and the prevention of recurrent Clostridium difficile infection. Although some data support the potential benefit of probiotic therapy in traveler's diarrhea, diverticular disease, and Helicobacter pylori, the strength of this evidence is limited. This paper will review the recent literature relevant to the mechanism of action and utility of probiotics and prebiotics in the treatment of gastrointestinal infections.

Journal Article↗
PubMed2006

Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium difficile diarrhea.

Antibiotic-associated diarrhea is a common clinical problem occurring in up to 25% of patients, with diarrhea owing to Clostridium difficile accounting for up to a quarter of cases. The clinical and economic costs of antibiotic-associated diarrhea are significant and better treatments are needed. Probiotics may offer potential effective therapy for antibiotic-associated diarrhea by restoring intestinal microbial balance. A number of different probiotics have been evaluated in the prevention and treatment of antibiotic-associated diarrhea in adults and children, including the nonpathogenic yeast Saccharomyces boulardii and multiple lactic-acid fermenting bacteria such as Lactobacillus rhamnosus GG (LGG). A careful review of the literature supports the efficacy of S. boulardii in the prevention of antibiotic-associated diarrhea recurrent C. difficile infection in adults, whereas LGG is useful in the treatment of antibiotic-associated diarrhea in children. Not enough data exist to currently support the use of other probiotic preparations in these conditions. Although generally safe and well tolerated, both S. boulardii and LGG should be used cautiously in immunocompromised patients. Further study of probiotics, including large, well-designed, randomized controlled dose-ranging trials, comparative trials, and cost-benefit analyses are necessary.

Anti-Bacterial Agents↗
PubMed2004

Treatment of inflammatory bowel disease with corticosteroids.

Corticosteroids are a mainstay in the treatment of inflammatory bowel disease. Administered topically, orally, or intravenously corticosteroids rapidly and consistently improve moderate to severe active ulcerative colitis and Crohn's disease, although they are ineffective in the maintenance of remission in either illness. The beneficial effects of corticosteroid therapy are counterbalanced by their many side effects. A better understanding of the mechanism of steroid action and toxicity has led to the development of novel corticosteroids that offer the promise of continued efficacy with minimal toxicity. This article reviews the role of conventional and novel corticosteroids in the management of inflammatory bowel disease.

Adrenal Cortex Hormones↗
PubMed2004

Pregnancy and inflammatory bowel disease.

PURPOSE OF REVIEW: Inflammatory bowel disease commonly affects women during the childbearing years, and young couples are often concerned about the potential effects of inflammatory bowel disease on fertility, pregnancy, and the fetus. This review will critically consider advances over the past 2 years in our knowledge of the effects of inflammatory bowel disease on fertility and pregnancy outcome and the safety and efficacy of medical therapy in the pregnant woman with inflammatory bowel disease. RECENT FINDINGS: The past several years have witnessed significant additions to our knowledge of the effects of ulcerative colitis and Crohn disease on fetal outcome. In addition, important studies have added to the growing database pointing to the overall safety of medical therapy with aminosalicylates and immunomodulators during pregnancy. Limited new data also suggest that inadvertent exposure to infliximab appears not to be harmful to the fetus. SUMMARY: Women with Crohn disease appear to be at risk for early delivery and low birthweight infants, and women with ulcerative colitis may be at increased risk for giving birth to children with congenital abnormalities. The clinical significance of these results may be diluted, however, by inability to adequately assess the confounding influence of disease activity or drug treatment. Despite lingering concerns, the most recent data support the overall safety of the 5-aminosalicylate drugs as well as azothiaprine/6-mercaptopurine during pregnancy. Despite these advances, the potential complications of inflammatory bowel disease and its therapies during pregnancy continue to require careful discussion with each individual couple before conception.

Journal Article↗
PubMed2004

Outcome of pregnancy in women receiving infliximab for the treatment of Crohn's disease and rheumatoid arthritis.

OBJECTIVES: Infliximab is approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). We report the first large series of pregnancy outcomes in women with RA and CD exposed to infliximab. METHODS: The infliximab safety database was queried for all reports of pregnancy. Data were extracted regarding the indication for infliximab, timing of infliximab relative to conception, pregnancy course, and pregnancy outcome. The proportion of live births, miscarriages, and therapeutic terminations for women directly exposed to infliximab before or during confirmed pregnancy were compared to those expected for the general U.S. population of pregnant women and pregnant women with CD not exposed to infliximab. RESULTS: Of the 146 identified pregnancies, 131 involved women exposed directly to infliximab and outcome data were available for 96 of these women. Live births occurred in 67% (64/96), miscarriages in 15% (14/96), and therapeutic termination in 19% (18/96) of the pregnancies directly exposed to infliximab with available outcome data. These results are similar to those expected for the general U.S. population of pregnant women or pregnant women with CD not exposed to infliximab. CONCLUSION: Data from the infliximab safety database suggest that infliximab exposure during pregnancy results in outcomes that do not differ from those in the U.S. population of pregnant women and pregnant women with CD not exposed to infliximab. No increased risk of adverse outcome was detected, however, follow-up of larger numbers of pregnant women exposed to infliximab will be necessary to definitively exclude any fetal risk.

Adolescent↗
PubMed2003

Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients.

BACKGROUND & AIMS: Platelets circulate in an activated state in patients with inflammatory bowel disease (IBD), but their role in the pathogenesis of IBD is unclear. The recent demonstration that activated platelets express CD40 ligand (L) provides a mechanism of interaction with CD40-positive endothelial cells, inducing them to produce proinflammatory mediators. We investigated whether platelets from patients with IBD express enhanced levels of CD40L and induce human intestinal microvascular endothelial cells (HIMEC) to up-regulate cell adhesion molecule (CAM) expression and secrete chemokines. METHODS: CD40L expression was assessed in resting and thrombin-activated platelets by flow cytometry and in mucosal microthrombi by confocal microscopy. Platelet-HIMEC cocultures were used to study CAM up-regulation, and interleukin (IL)-8 and RANTES production by HIMEC. RESULTS: IBD platelets expressed significantly higher CD40L levels than those of healthy subjects, and CD40L-positive platelets were detected in IBD-involved mucosa. Activated platelets up-regulated expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 as well as production of interleukin 8 by HIMEC in a CD40-dependent fashion. High levels of RANTES were present in platelet-HIMEC cocultures and platelets were identified as the source of this chemokine, which mediated T-cell adhesion to HIMEC. CONCLUSIONS: These results show that platelets can actively contribute to mucosal inflammation and represent a previously unrecognized component of IBD pathogenesis.

Blood Platelets↗
PubMed2002

Endoscopy in the pregnant patient with inflammatory bowel disease.

Although little data exist directly evaluating the utility and safety of endoscopy in the pregnant woman with IBD, it appears to be well tolerated by both mother and fetus, and provides useful clinical information. When performed to evaluate gastrointestinal bleeding, EGD has a high diagnostic yield, while EGD for nausea and vomiting is less informative. In the patient without IBD presenting with hematochezia, unexplained diarrhea, severe abdominal pain, or severe rectal pain, careful sigmoidoscopic examination is indicated, often leading to a diagnosis of new-onset or unsuspected IBD. Likewise, the pregnant IBD patient with worsening symptoms, despite appropriate medical therapy, may also benefit from sigmoidoscopy. Colonoscopy is less often indicated, but can be safely performed in the carefully selected pregnant patient. In all cases obstetrical consultation should be obtained prior to endoscopy, and the risks and benefits of endoscopy to both mother and child should be considered. Close attention should be paid to appropriate drug selection for conscious sedation, and sedation should be administered to provide patient comfort, while avoiding oversedation. Extrapolating from data obtained during endoscopic examination of the pregnant non-IBD patient, fetal monitoring is generally not indicated, although it should be considered for the high-risk or late third-trimester patient. Following these principles assures that endoscopy can be safely performed in the pregnant IBD patient with the best possible outcome for both mother and baby.

Procedural Sedation↗
PubMed2002

Inflammatory bowel disease.

Although inflammatory bowel disease (IBD) usually presents in adolescents and young adults, both ulcerative colitis and Crohn's disease can also present in older adults. The diagnosis of IBD in the elderly is often difficult and can easily be confused with diverticulitis or ischaemic colitis. The symptoms and complications of IBD in the elderly are similar to those found in younger patients. However, when IBD presents later in life the disease is often less extensive and milder. Older IBD patients are treated with the same medications as younger patients, although the risk for drug toxicity is greater, especially with corticosteroid therapy. Comorbid illness in older patients often has a significant impact on the outcome of medical and surgical therapy for IBD but, in the absence of significant co-morbid disease, most elderly IBD patients can expect a good response to therapy.

Aged↗
PubMed2002

Advances in the medical therapy of inflammatory bowel disease.

The medical therapy of inflammatory bowel disease (IBD) has advanced significantly over the past year. Serologic markers of IBD have been further investigated and better defined, showing some discriminatory power with potential therapeutic implications. Studies of azathioprine and 6-mercaptopurine metabolites will make it easier and safer to use these effective drugs. Clinical data using other immunomodulators, including 6-thioguanine, mycophenolate mofetil, cyclosporine, and tacrolimus, continue to accrue with positive results. Infliximab has become even more firmly established as a reliable and effective therapy for active and fistulizing Crohn disease and may even be helpful in some patients with resistant ulcerative colitis. However, the recognition of potential complications of infliximab therapy has increased with the accumulated clinical experience. Results from trials of other biologic therapies directed at tumor necrosis factor alpha have been disappointing so far, although preliminary studies with biologics directed at adhesion molecules are encouraging. Growing appreciation of the importance of the enteric microflora in IBD has led to a considerable interest in manipulating intestinal bacteria for therapeutic benefit, and trials of both probiotics and prebiotics show promise.

Journal Article↗